N-fluoromethyl-carbamic acid fluorides and their manufacture

ABSTRACT

New N-fluoromethyl-carbamic acid fluorides and a new process for their manufacture by reacting N-halomethyl-carbamic acid halides with metal fluorides. The products are starting materials for the manufacture of drugs, dyes, pesticides, plastics, plastics auxiliaries and textile auxiliaries.

The present invention relates to new N-fluoromethyl-carbamic acidfluorides and a new process for their manufacture by reactingN-halomethyl-carbamic acid halides with metal fluorides.

Houben-Weyl, Methoden der Organischen Chemie, Volume V/3, page 148discloses that the reaction of carboxylic acid chlorides with potassiumfluoride to give carboxylic acid fluorides is substantially moredifficult than the reaction of sulfochlorides with potassium fluoride togive sulfofluorides; glacial acetic acid and acetic anhydride arerecommended as the reaction medium for achieving a satisfactory yield.If a halocarboxylic acid chloride is heated with potassium hydrogenfluoride on a waterbath (Houben-Weyl, loc. cit., pages 149 and 150), thecorresponding halocarboxylic acid fluoride is obtained. The halogenpresent as an α-substituent in the carboxylic acid is not split offduring the reaction, so that, for example, chloroacetyl fluoride,dichloroacetyl fluoride, trichloroacetyl fluoride, bromoacetyl fluorideor iodoacetyl fluoride is formed from the corresponding chloride.

The manufacture of N-fluoromethyl-carbamic acid fluorides has notpreviously been disclosed.

α-Haloalkyl-carbamic acid halides are at one and the same time acidhalides and α-Haloalkylamines, i.e. they contain two reactive centers.α-haloalkylamines are very reactive compounds, and acid halides are alsoknown to be extremely reactive. It could therefore not be foreseen whichof the two reactive halogen atoms would react with a metal fluoride, andto what degree.

We have found that an N-fluoromethyl-carbamic acid fluoride of theformula ##STR1## where R¹ is a cycloaliphatic radical or is ##STR2## R²,R³ and R⁴ may be identical or different and each is hydrogen or analiphatic radical, and in addition R² may be fluorine if R³ and R⁴ areeach hydrogen is obtained in an advantageous manner if ahalomethyl-carbamic acid halide of the formula ##STR3## where theindividual radicals X are each chlorine or bromine and R⁵ has the samemeaning as R¹ or, if R² is fluorine, may also represent ##STR4## where Xhas the above meaning, is reacted with a fluoride of a metal of groupIa, Ib, IIa, IIb, IIIa, IIIb, IVa, IVb, Va, VIb, VIIb or VIIIb of theperiodic table.

Further, we have found the new N-fluoromethyl-carbamic acid fluorides ofthe formula ##STR5## where R¹ is a cycloaliphatic radical or is ##STR6##R², R³ and R⁴ may be identical or different and each is hydrogen or analiphatic radical, in addition R² may be fluorine if R³ and R⁴ are eachhydrogen.

Where N-chloromethyl-N-methyl-carbamic acid chloride and potassiumfluoride are used, the reaction may be represented by the followingequation: ##STR7##

The process of the invention is surprising in view of the prior art andgives N-fluoromethyl-carbamic acid fluorides in a simple and economicalmanner, in good yield and high purity. In view of the conventionalprocesses, it was not to be expected that fluorine would replace theoriginal halogen substituted both on the α-carbon atom and on the acidhalide group. Equally, increased formation of byproducts anddecomposition products might have been expected in view of thereactivity of both the fluorine and the carbamido group. It is thereforesurprising that a high yield of a pure, single end product is obtainedin place of the heterogeneous mixture of numerous components which mighthave been expected.

The starting materials II can easily be manufactured, for example by theprocesses disclosed in German Published Application DAS 1,154,087(reaction of a carbamic acid chloride or carbamic acid bromide withbromine or chlorine), German Published Application DAS 1,153,756(reaction of 1,3,5-trialkylhexahydro-s-triazines with haloacylcompounds) and German Laid-Open Appliction DOS 2,043,235 (reaction of aSchiff base with phosgene). Preferred starting materials II andaccordingly preferred end products I are those where R¹ is cycloalkyl of5 to 8 carbon atoms or is ##STR8## R², R³ and R⁴ may be identical ordifferent and each is hydrogen or alkyl of 1 to 20, especially of 1 to7, carbon atoms or alkenyl of 2 to 20, especially of 2 to 7, carbonatoms, in addition R² may also be fluorine if R³ and R⁴ are eachhydrogen, the individual radicals X are different or, preferably,identical, and each is chlorine or bromine and R⁵ has the meaning of R¹or, if R² is fluorine, may also be ##STR9## where X has the abovemeaning. The above radicals may in addition be substituted by groupswhich are inert under the reaction conditions, e.g. alkyl of 1 to 4carbon atoms.

Examples of suitable starting materials II are N-methyl-, N-ethyl-,N-n-propyl-, N-isopropyl-, N-n-butyl-, N-isobutyl-, N-sec.-butyl-,N-tert.-butyl-, N-pentyl-, N-isopentyl-, N-hexyl-, N-heptyl-, N-octyl-,N-isooctyl-, N-allyl-, N-crotyl-, N-undec-11-en-1-yl-, N-oleyl-,N-cyclopentyl-, N-cyclohexyl-, N-cycloheptyl-, N-cycloocytyl-,N-fluoromethyl- and N-bromomethyl-N-chloromethyl-carbamic acid chloride,N,N-bis-(chloromethyl)-carbamic acid chloride and the correspondingN-bromomethyl-carbamic acid bromides; preferred starting materials areN-chloromethyl-N-methyl-carbamic acid chloride,N,N-bis-(chloromethyl)-carbamic acid chloride,N-chloromethyl-N-isopropyl-carbamic acid chloride,N-chloromethyl-N-tert.-butyl-carbamic acid chloride andN-chloromethyl-N-cyclohexyl-carbamic acid chloride.

The other starting materials used are metal fluorides of metals ofgroups Ia, Ib, IIa, IIb, IIIa, IIIb, IVa, IVb, Va, VIb, VIIb and VIIIb,preferably of groups Ia, IIa, IIIa, IVa, Va and IIb, of the periodictable. The groups mentioned are as defined in D'Ans-Lax, Taschenbuch furChemiker und Physiker (Springer, Berlin, 1967), Volume 1, page 63(corresponding to Weast, Handbook of Chemistry and Physics (The ChemicalRubber Co., Cleveland, 50th ed.), page B 3, and Clark, The Encyclopaediaof Chemistry, 2nd edition (Reinhold Pub. Corp., N.Y., 1966), page 790).Advantageous fluorides to use are sodium fluoride, potassium fluoride,potassium hydrogen fluoride, sodium hydrogen fluoride, lithium fluoride,calcium fluoride, barium fluoride, magnesium fluoride, silver(I)fluoride, silver(II) fluoride, zinc(II) fluoride, mercury(I) fluoride,mercury(II) fluoride, cadmium(II) fluoride, beryllium(II) fluoride,copper(II) fluoride, boron(III) fluoride, aluminum(III) fluoride,cerium(III) fluoride, thallium(I) fluoride, zirconium(IV) fluoride,titanium(III) fluoride, titanium(IV) fluoride, tin(II) fluoride, tin(IV)fluoride, lead(II) fluoride, lead(IV) fluoride, arsenic(III) fluoride,arsenic(V) fluoride, antimony(III) fluoride, antimony(V) fluoride,bismuth(V) fluoride, molybdenum(III) fluoride, molybdenum(IV) fluoride,uranium(IV) fluoride, uranium(VI) fluoride, manganese(II) fluoride,manganese(III) fluoride, iron(II) fluoride, iron(III) fluoride,cobalt(II) fluoride and cobalt(III) fluoride. KF, KHF₂, CaF₂, NaF,NaHF₂, MgF₂, and SbF₃ are preferred. The metal fluoride may be used inthe stoichiometric amount or in excess, advantageously in an amount offrom 1 to 3 equivalents of metal fluoride per halogen atom of thecarbamic acid halide group and of the α-carbon atoms of startingmaterial II. Accordingly, the stoichiometric requirement is 2equivalents of fluoride, e.g. 2 moles of KF or 1 mole of CaF₂, per moleof monohalomethyl-carbamic acid halide, and 3 equivalents of fluoride,e.g. 1 mole of AlF₃ or 1.5 moles of CaF₂, per mole of dihalomethylcompound II.

The reaction is as a rule carried out at from 40° to 300° C., preferablyfrom 60° to 200° C., especially from 95° to 162° C., under atmosphericor superatmospheric pressure, continuously or batchwise. It isadvantageous to use organic solvents which are inert under the reactionconditions, examples being ethers, e.g. ethyl propyl ether, methyltert.-butyl ether, N-butyl ethyl ether, di-n-butyl ether, diisobutylether, diisoamyl ether, diisopropyl ether, anisole, phenetole,cyclohexyl methyl ether, diethyl ether, tetrahydrofuran, dioxane,thioanisole and β,β'-dichlorodiethyl ether, polyethylene glycol ethers,e.g. ethylene glycol dimethyl ether, diethyl ether, di-n-propyl ether,diisopropyl ether, di-n-butyl ether, diisobutyl ether, di-sec.-butylether and di-tert.-butyl ether, diethylene glycol dimethyl ether,diethyl ether, di-n-propyl ether, diisopropyl ether, di-n-butyl ether,diisobutyl ether, di-sec.-butyl ether and di-tert.-butyl ether, andcorresponding diethers of triethylene glycol and of tetraethyleneglycol, sulfoxides, e.g. dimethylsulfoxide and diethylsulfoxide,dimethyl sulfone, diethyl sulfone, methyl ethyl sulfone andtetramethylene sulfone (sulfolan), N-methylpyrrolidone,dimethylformamide, hexamethylphosphorotriamide and mixtures of these.Advantageously, the solvent is used in an amount of from 400 to 10,000percent by weight, preferably from 500 to 2,000 percent by weight, basedon starting material II.

The reaction may be carried out as follows: a mixture of the startingmaterial II, a metal fluoride and, advantageously, a solvent is kept atthe reaction temperature for from 1/2 to 10 hours. In one embodiment,the process may be carried out by adding the carbamic acid halidereactant, which may or may not be dissolved in a solvent, to a solutionor suspension containing the metal fluoride and heating the mixture tothe reaction temperature. However, it is more advantageous to heat themetal fluoride solution or suspension to the reaction temperature andadd the carbamic acid halide slowly so as to keep the temperatureconstant. The end product is then isolated from the reaction mixture inthe conventional manner, e.g. by fractional distillation.

The new compounds which may be manufactured by the process of theinvention are valuable starting materials for the manufacture of drugs,dyes, pesticides, plastics, plastics auxiliaries and textileauxiliaries. For example, reaction of the end products I with phenols oramines gives, respectively, the corresponding carbamates or ureas, whichare valuable active ingredients of, for example, herbicides andfungicides (Examples 6 to 8). Reaction of the end products I withalkenols gives valuable starting materials for the manufacture ofcoating intermediates, plastics, paints and crop protection agents. Theproducts can be copolymerized with other monomers, e.g. acrylic acidesters, methacrylic acid esters and styrene. Regarding thecopolymerization, reference may be made to Houben-Weyl, Methoden derOrganischen Chemie, Volume 14/1, page 24 (1961). The copolymers may beused with advantage as coatings or films on building materials, e.g. onwood, stone or concrete surfaces. Such coatings or films can be producedby any desired conventional method (Ullmanns Encyclopadie dertechnischen Chemie, Volume 11, pages 283 and 367 et seq. (1960)).Equally, the products obtained from alkenols and the compounds I can beused to produce, by polymerization, advantageous crosslinking agents forpolyamines. The polyamines are crosslinked by, for example, theprocesses described in Houben-Weyl, loc. cit. The products obtained byreacting the compounds I with alcohols and/or water can be reacted withdiamines or polyamines to give urea compounds which are valuableantistatic agents. Reaction of the end products I with tribromoanilinegives urea derivatives with flameproofing properties. For the aboveuses, it is advantageous to employ the preferred end products, inparticular N-fluoromethyl-N-methyl-carbamic acid fluoride,N,N-bis-(fluoromethyl)-carbamic acid fluoride,N-fluoromethyl-N-isopropyl-carbamic acid fluoride,N-fluoromethyl-N-tert.-butyl-carbamic acid fluoride andN-fluoromethyl-N-cyclohexyl-carbamic acid fluoride.

In the Examples which follow, parts are by weight, and bear the samerelation to parts by volume as that of the kilogram to the liter.

EXAMPLE 1

139 parts of potassium fluoride are suspended in 300 parts by volume ofsulfolan and heated to 160° C., with vigorous stirring. At thistemperature, 85 parts of N-chloromethyl-N-methyl-carbamic acid chlorideare added whilst keeping the temperature constant. The mixture is thenstirred for a further 2 hours at 160° C., after which it is distilled.45 parts (69% of theory) of N-fluoromethyl-N-methyl-carbamic acidfluoride of boiling point 37°-38° C./27 mm Hg and refractive index n_(D)²⁵ =1.375 are obtained.

EXAMPLE 2

348 parts of potassium fluoride are suspended in 500 parts by volume ofsulfolan and the mixture is heated to 140° C. 160 parts ofN,N-bis-(chloromethyl)-carbamic acid chloride are added at from 130° to140° C. whilst keeping the temperature constant. The mixture is thenleft at from 130° to 140° C. for a further 3 hours. After fractionaldistillation under reduced pressure, 57 parts (50% of theory) ofN,N-bis-(fluoromethyl)-carbamic acid fluoride of boiling point 56° C./35mm Hg and refractive index n_(D) ²⁰ =1.366 are obtained.

EXAMPLE 3

174 parts of potassium fluoride are suspended in 200 parts by volume ofsulfolan and the suspension is heated to 120° C., at which temperature166 parts of N-tert.-butyl-N-chloromethyl-carbamic acid chloride areadded. The mixture is stirred for a further 2 hours at 120° C. and thendistilled. 93 parts (68% of theory) ofN-tert.-butyl-N-fluoromethyl-carbamic acid fluoride of refractive indexn_(D) ²³ =1.398 and boiling point 90° C./77 mm Hg are obtained.

EXAMPLE 4

743 parts of potassium fluoride in 800 parts by volume of sulfolan areheated to 100° C., and at this temperature 530 parts ofN-chloromethyl-N-isopropyl-carbamic acid chloride are added. After 2.5hours, the mixture is distilled. 295 parts (69% of theory) ofN-fluoromethyl-N-isopropyl-carbamic acid fluoride of refractive indexn_(D) ²¹ =1.389 and boiling point 50° C./13 mm Hg are obtained.

EXAMPLE 5

188 parts of potassium fluoride in 200 parts by volume of sulfolan areheated to 100° C. and whilst keeping this temperature constant, 170parts of N-chloromethyl-N-cyclohexyl-carbamic acid chloride are added.The mixture is stirred for a further 2.5 hours at 100° C. and is thendistilled under reduced pressure. 81 parts (57% of theory) ofN-fluoromethyl-N-cyclohexyl-carbamic acid fluoride of refractive indexn_(D) ²² =1.441 and boiling point 45° C./0.01 mm Hg are obtained.

EXAMPLE 6 (USE) (a) O-3-Isopropyl-5-methyl-phenylN,N-bis-fluoromethyl-carbamate

16 parts of 80 percent strength by weight 3-isopropyl-5-methyl-phenol in30 parts of methylene chloride are added to 12.7 parts ofN,N-bis-fluoromethyl-carbamic acid fluoride (from Example 2) in 50 partsof methylene chloride. 10.1 parts of triethylamine in 20 parts ofmethylene chloride are then added. The reaction mixture is stirred forone hour at 40° C. and when it has cooled it is extracted by shakingwith 10 percent strength by weight sodium hydroxide solution and water,dried and distilled to dryness under reduced pressure. 24.1 parts (95%of theory) of O-3-isopropyl-5-methyl-phenylN,N-bis-fluoromethyl-carbamate of boiling point 120° C./0.05 mm Hg areobtained.

(b) 5 ml of double-strength nutrient broth are added to 5 ml of an 0.2percent strength solution of O-3-isopropyl-5-methylphenylN,N-bis-fluoromethyl-carbamate in water, in a sterile test tube, and thecomponents are mixed. The contents of the test tube are then inoculatedwith one drop of a 16 hours' old Staphylococcus aureus culture which hasbeen diluted 1:10, and are incubated for 72 hours at 37° C. After thistime, samples are transferred from the test tube to nutrient media forbacteria and these are incubated for 24 hours at 37° C. The nutrientmedia treated with the samples contain 100 ppm of active ingredient insuspension. After transfer to the nutrient media for bacteria, nobacterial growth is detectable in the samples containing the aboveactive ingredient, in contrast to the controls to which the activeingredient has not been added.

EXAMPLE 7 (USE) (a) O-3,5-Dichloro-phenyl N,N-bis-fluoromethyl-carbamate

16.3 parts of 3,5-dichlorophenol and 15.3 parts ofN,N-dimethylcyclohexylamine are introduced into 100 parts of toluene.12.7 parts of N,N-bis-fluoromethyl-carbamic acid fluoride (from Example2) are added in portions at from 10° to 22° C., with thorough mixing.The batch is then stirred for 20 minutes at 70° C. When it has cooled,the mixture is extracted by shaking with 10 percent strength by weightsodium hydroxide solution and with water, and is dried, and distilled todryness under reduced pressure. 25.8 parts of O-3,5-dichlorophenylN,N-bis-fluoromethyl-carbamate (70% of theory), having a melting pointof 76°-78° C. after recrystallization from cyclohexane, are obtained.(b) 5 ml of double-strength nutrient broth are added to 5 ml portions ofan 0.2 percent strength solution of the end product from Example 7(a) inwater, in a sterile test tube, and the components are mixed. Thecontents of the test tube are then inoculated with one drop of a 16hours' old Staphylococcus aureus culture which has been diluted 1:10,and are incubated for 72 hours at 37° C. After this time, samples aretransferred from the test tube to nutrient media for bacteria and theseare incubated for 24 hours at 37° C. The nutrient media treated with thesamples contain 100 ppm of active ingredient in suspension. Aftertransfer to the nutrient media for bacteria, no bacterial growth isdetectable in the samples containing the above active ingredient, incontrast to the controls to which the active ingredient has not beenadded.

EXAMPLE 8 (USE) (a)N,N-Bis-fluoromethyl-N'-methyl-N'-(2-benzthiazolyl)-urea

4 parts of a mixture of 80 parts of sodium hydride and 20 parts of whiteoil are introduced into 50 parts of tetrahydrofuran. 21.4 parts of2-(methylamino)-benthiazole in 250 parts of tetrahydrofuran are added inportions at from 25° to 35° C. The reaction mixture is stirred for 2hours at 40° C. and 17 parts of N,N-bis-fluoromethylcarbamic acidfluoride (from Example 2) are then added at 22° C. After 4 hours, themixture is filtered, the filtrate is concentrated under reduced pressureand the residue is stirred with ethyl acetate. 1.5 parts ofN,N-bis-fluoromethyl-N'-methyl-N'-(2-benzthiazolyl)-urea of meltingpoint 131°-134° C. are obtained. (b) The end product from Example 8(a)is tested for its herbicidal and fungicidal properties. It possesses agood herbicidal action which manifests itself particularly when used inconnection with crops; the latter are not damaged.

We claim:
 1. A process for the manufacture of a N-fluoromethyl-carbamicacid fluoride of the formula ##STR10## where R¹ is a cycloaliphaticradical or is ##STR11## where R², R³ and R⁴ may be identical ordifferent and each is hydrogen or an aliphatic radical, and in additionR² may be fluorine if R³ and R⁴ are each hydrogen, wherein ahalomethyl-carbamic acid halide of the formula ##STR12## where theindividual radicals X are each chlorine or bromine and R⁵ has the samemeaning as R¹ or, if R² is fluorine, may also represent ##STR13## whereX has the above meaning, is reacted at from 40° to 300° C. with afluoride of a metal of groups Ia, Ib, IIa, IIb, IIIa, IIIb, IVa, IVb,Va, VIb, VIIb and VIIIb of the periodic table.
 2. The process of claim1, wherein the reaction is carried out with sodium fluoride, potassiumfluoride, potassium hydrogen fluoride, sodium hydrogen fluoride, lithiumfluoride, calcium fluoride, barium fluoride, magnesium fluoride,silver(I) fluoride, silver(II) fluoride, zinc(II) fluoride, mercury(I)fluoride, mercury(II) fluoride, cadmium(II) fluoride, beryllium(II)fluoride, copper(II) fluoride, boron(III) fluoride, aluminum(III)fluoride, cerium(III) fluoride, thallium(I) fluoride, zirconium(IV)fluoride, titanium(III) fluoride, titanium(IV) fluoride, tin(II)fluoride, tin(IV) fluoride, lead(II) fluoride, lead(IV) fluoride,arsenic(III) fluoride, arsenic(V) fluoride, antimony(III) fluoride,antimony(V) fluoride, bismuth(V) fluoride, molybdenum(III) fluoride,molybdenum (IV) fluoride, uranium(IV) fluoride, uranium(VI) fluoride,manganese (II) fluoride, manganese(III) fluoride, iron(II) fluoride,iron(III) fluoride, cobalt(II) fluoride and/or cobalt(III) fluoride. 3.The process of claim 1, wherein the reaction is carried out with from 1to 3 equivalents of metal fluoride per halogen atom of the carbamic acidhalide group and of the α-carbon atoms of the starting material II. 4.The process of claim 1, wherein the reaction is carried out at from 60°to 200° C.
 5. The process of claim 1, wherein the reaction is carriedout with from 400 to 10,000 percent by weight, based on startingmaterial II, of an organic solvent which is inert under the reactionconditions.